DESCRIPTION (Taken directly from applicant's abstract) There is now considerable evidence that chronic hyperlipidemia is a significant risk factor for progressive renal injury in both experimental animals and humans with treatment-resistant nephrotic syndrome (NS). The extent to which this process can be interrupted by treating the hyperlipidemia with a combination of diet and a lipidlowering medication in children with resistant NS is not known. The present application describes a pilot study that is designed to assess the feasibility of studying this question in a large multicenter, randomized, clinical trial. The primary goal of our pilot study is to evaluate the safety and efficacy of treating hyperlipidemia (LDL cholesterol >160 mg/dl) in children with NS, in whom renal function is relatively well-preserved (GFR 230% of normal), but in whom proteinuria and hyperlipidemia persist after other appropriate measures to treat their primary disease have been exhausted. The agent to be tested is a new potent HMG-CoA reductase inhibitor (atorvastatin). Patients who enter this study will undergo a three month equilibration period. During this period, we will establish the patients on a low-cholesterol diet, ensure the patients do not have a rapidly progressive form of nephropathy, and wash out the effect of any lipid-lowering or other excluded drugs given to them before randomization. After three months of diet, the patients will be assigned to either treatment with atorvastatin or a placebo. The patients will then be followed for three months with serial measurements comparing lipid profiles, chemistry panels, and protein excretion in treated and control patients. Following the three month randomized period, all patients will be converted to atorvastatin for an additional 6-9 months. The study will be conducted in 15 clinical centers where patients will be recruited and studied, and will be coordinated by a Data/Administrative Coordinating Center in Dallas, Texas. Although the primary goal of this study is to determine the safety and efficacy of atorvastatin for treating children with resistant NS and hyperlipidemia, our studies are also designed to provide preliminary data for a future investigation into the potential effect that lowering cholesterol levels may have on the rate of progression of renal insufficiency in such patients.